Received 12 August 2009; accepted 16 October 2009; published online 20 October 2009

Abstract - The principal surveillance tool used to control bovine
tuberculosis in cattle is the removal of
animals that provide a positive response to the tuberculin skin-test. In
this study we performed a
longitudinal investigation of the immunological and diagnostic consequences
of repeated short-interval
skin-tests in cattle naturally infected with Mycobacterium bovis. Tuberculin
skin-test positive cattle were
subjected to up to four further intradermal comparative cervical skin-tests
at approximately 60-day intervals.
A significant progressive reduction in the strength of the skin-test was
observed after successive tests. In
contrast, the magnitude of interferon- (IFN-) responses was not influenced
by repeat skin-testing either
transiently around the time of each skin-test or longitudinally following
repeated tests. A significant boost in
blood interleukin-10 (IL-10) production was observed within 3 days following
each skin-test although the
magnitude of this boosted response returned to lower levels by day 10
post-test. The application of a novel
multiplex assay to simultaneously measure seven cytokines and chemokines
also identified that skin-testing
resulted in a significant and progressive reduction in antigen specific
interleukin-1 (IL-1) whilst
confirming stable IFN- and elevated IL-10 responses in the blood.
Therefore, we have demonstrated that in
cattle naturally infected with M. bovis, repeat short-interval skin-testing
can lead to a progressive reduction
in skin-test responsiveness which has potential negative consequences for
the detection of infected animals
with marginal or inconclusive skin-test responses. The desensitising effect
is associated with decreased
IL-1 and elevated IL-10 responses, but importantly, does not influence
antigen specific IFN- responses.